Dysregulation of lysosome/mitochondrial interaction in obese adipose tissue

2020 Fiscal Year Final Research Report

• Project/Area Number: 17H02179
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied health science
• Research Institution: Tokyo University of Science
• Principal Investigator: Higami Yoshikazu 東京理科大学, 薬学部生命創薬科学科, 教授 (90253640)
• Co-Investigator(Kenkyū-buntansha): 小林 正樹 東京理科大学, 薬学部生命創薬科学科, 助教 (30795612) ; 中川 嘉 筑波大学, 国際統合睡眠医科学研究機構, 准教授 (80361351) ; 沖田 直之 山陽小野田市立山口東京理科大学, 薬学部, 講師 (60453841) ; 野口 満 佐賀大学, 医学部, 教授 (00325648)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 肥満症 / カロリー制限 / 脂肪組織 / ミトコンドリア生合成 / ミトファジー / PARIS

Outline of Final Research Achievements

Both PARKIN and PINK1, which are involved in the onset of hereditary Parkinson's disease via mitophagy defect, interact with and PARIS. We found that these proteins highly expressed in white adipose tissue (WAT). It has also been reported that PARIS binds to the Pgc-1α promoter, which is a major transcriptional cofactor involved in mitochondrial biosynthesis, negatively regulates its expression. We have shown that the expression of PARIS is increased in obese WAT, decreased by caloric restriction showing antiaging and prolongevity effects. Moreover, mitochondrial biosynthesis was reduced in PARIS overexpressing adipocytes. Therefore, our observation suggested that PARIS might be a balance regulator between mitochondrial biosynthesis and clearance in WAT.

Free Research Field

分子病理・代謝学

Academic Significance and Societal Importance of the Research Achievements

肥満症やそれにともなって発症する生活習慣病の発症予防は、超高齢化社会を迎える本邦においてはもっとも重要かつ喫緊の課題である。我々の研究成果はミトコンドリアの質の改善を介する脂肪組織の質の向上、ひいては肥満症における代謝改善、生活習慣病の予防、さらに心筋梗塞や脳血管障害の予防に通ずる、貴重な研究成果であると考えられる。